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The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation.
- Source :
-
PloS one [PLoS One] 2013 Jul 01; Vol. 8 (7), pp. e68247. Date of Electronic Publication: 2013 Jul 01 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- The Notch signaling pathway controls diverse cell-fate specification events throughout development. The versatility of this pathway to influence different aspects of development comes from its multiple levels of regulation. Upon ligand-induced Notch activation, the Notch intracellular domain (Notch-ICD) is released from the membrane and translocates to the nucleus, where it transduces Notch signals by regulating the transcription of downstream target genes. But the exact mechanism of translocation of Notch-ICD into the nucleus is not clear. Here, we implicate Importin-α3 (also known as karyopherin-α3) in the nuclear translocation of Notch-ICD in Drosophila. Our present analyses reveal that Importin-α3 can directly bind to Notch-ICD and loss of Importin-α3 function results in cytoplasmic accumulation of the Notch receptor. Using MARCM (Mosaic Analysis with a Repressible Cell Marker) technique, we demonstrate that Importin-α3 is required for nuclear localization of Notch-ICD. These results reveal that the nuclear transport of Notch-ICD is mediated by the canonical Importin-α3/Importin-β transport pathway. In addition, co-expression of both Notch-ICD and Importin-α3 displays synergistic effects on cell proliferation. Taken together, our results suggest that Importin-α3 mediated nuclear import of Notch-ICD may play important role in regulation of Notch signaling.
- Subjects :
- Active Transport, Cell Nucleus
Animals
Cell Nucleus metabolism
Cell Proliferation
Drosophila Proteins genetics
Drosophila melanogaster genetics
Mutation
Receptors, Notch genetics
Signal Transduction
alpha Karyopherins genetics
Drosophila Proteins metabolism
Drosophila melanogaster cytology
Drosophila melanogaster metabolism
Receptors, Notch metabolism
alpha Karyopherins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23840889
- Full Text :
- https://doi.org/10.1371/journal.pone.0068247